Circadian variation in the head twitch response produced by 5-methoxy-N1,N1-dimethyltryptamine and p-chloroamphetamine in the mouse.
Psychopharmacology – January 01, 1981
Source: PubMed
Summary
Head twitch responses in male BK. TO mice displayed a clear circadian rhythm, peaking at specific times based on serotonin (5-HT) levels. After administering 400 mg/kg of p-chlorophenylalanine (PCPA), the number of twitches triggered by 5-methoxy-N1,N1-dimethyltryptamine (5-MeODMT) increased significantly on days 3 and 5, while levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), dropped. Interestingly, responses to p-chloroamphetamine (PCA) were highest during light periods when serotonin was abundant, highlighting the complex interplay between serotonin availability and receptor sensitivity throughout the day.
Abstract
Circadian fluctuations were measured in the head twitch response produced by 5-methoxy-N1,N1-dimethyltryptamine (5-MeODMT) and p-chloroamphetamine (PCA) in male BK. TO mice. The effects of depleting brain 5-hydroxytryptamine (5-HT) with p-chlorophenylalanine (PCPA) on the 5-MeODMT in the mouse were also studied. Changes in brain 5-HT and 5-hydroxyindoleacetic (5-HIAA) were concomitantly determined. PCPA (400 mg/kg IP twice on consecutive days) significantly increased the number of head twitches induced by 5-MeODMT (5 mg/kg IV) on days 3 and 5 after the initial injection of PCPA when 5-HT and 5-HIAA were also significantly reduced. On day 12, there was no significant difference in the number of head twitches between mice administered PCPA and those given saline, and 5-HT and 5-HIAA levels were nearly back to normal. PCPA, using the same dose schedule, significantly reduced the number of head twitches induced by PCA when PCA was administered 24 h after the second injection of PCPA (day 3. Mice maintained on a 12-h light-dark cycle showed a maximum response to the direct 5-HT receptor agonist 5-MeODMT (5 mg/kg IV) towards the end of the dark period, when the 5-HT level was at its lowest. p-Chloroamphetamine, which causes release of 5-HT from pre-synaptic neurones, produced a peak head twitch response in the middle of the light period when 5-HT and 5-HIAA levels were maximal, while the response towards the end of the dark period was significantly less than that at other times tested. It is concluded that 5-HT receptor response shows a circadian rhythm related to both pre-synaptic availability of 5-HT and post-synaptic receptor sensitivity.